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Stress, the Stress System and the Role of Glucocorticoids

A Puzserova, I Bernatova
Stress is considered a risk factor associated with the development of various civilization diseases including cardiovascular diseases, malignant tumors and mental disorders. Research investigating mechanisms involved in stress-induced hypertension have attracted much attention of physicians and researchers, however, there are still ambiguous results concerning a causal relationship between stress and long-term elevation of blood pressure (BP). Several studies have observed that mechanisms involved in the development of stress-induced hypertension include increased activity of sympathetic nervous system (SNS), glucocorticoid (GC) overload and altered endothelial function including decreased nitric oxide (NO) bioavailability...
October 24, 2016: Physiological Research
R A Bryant, K L Felmingham, B Liddell, P Das, G S Malhi
The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles...
October 18, 2016: Translational Psychiatry
L Caetano, H Pinheiro, P Patrício, A Mateus-Pinheiro, N D Alves, B Coimbra, F I Baptista, S N Henriques, C Cunha, A R Santos, S G Ferreira, V M Sardinha, J F Oliveira, A F Ambrósio, N Sousa, R A Cunha, A J Rodrigues, L Pinto, C A Gomes
Developmental risk factors, such as the exposure to stress or high levels of glucocorticoids (GCs), may contribute to the pathogenesis of anxiety disorders. The immunomodulatory role of GCs and the immunological fingerprint found in animals prenatally exposed to GCs point towards an interplay between the immune and the nervous systems in the etiology of these disorders. Microglia are immune cells of the brain, responsive to GCs and morphologically altered in stress-related disorders. These cells are regulated by adenosine A2A receptors, which are also involved in the pathophysiology of anxiety...
October 11, 2016: Molecular Psychiatry
Ingrid Nylander, Aniruddha Todkar, Linnea Granholm, Maria Vrettou, Megha Bendre, Wout Boon, Henrik Andershed, Catherine Tuvblad, Kent W Nilsson, Erika Comasco
Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans...
October 5, 2016: Molecular Neurobiology
Rebecca Dumbell, Alexei Leliavski, Olga Matveeva, Christopher Blaum, Anthony H Tsang, Henrik Oster
The circadian rhythm of glucocorticoids affects diverse physiological systems, including stress responses and the coordination of rhythmic functions in peripheral and central tissues. Circadian clocks are considered to be important coordinators of glucocorticoid release and loss of the core clock component BMAL1 leads to ablation of behavioural and physiological rhythms, hypocortisolism, impaired ACTH and behavioural stress responses. Transplantation and conditional clock gene knock-down studies in mice suggest an important role of local adrenocortical clock function in this context...
October 3, 2016: Endocrinology
Froylán Vargas-Martínez, Richard J Schanler, Steven A Abrams, Keli M Hawthorne, Susan Landers, José Guzman-Bárcenas, Onofre Muñoz, Tore Henriksen, Maria Petersson, Kerstin Uvnäs-Moberg, Ismael Jiménez-Estrada
Hypertension is a major risk factor for ischemic heart disease and stroke, leading causes of morbidity and death worldwide. Intrauterine growth restriction (IUGR), caused by an excess of glucocorticoid exposure to the fetus, produces an imbalance in oxidative stress altering many biochemical and epigenetic gene transcription processes exposing the fetus and neonate to the 'thrifty' phenotype and pervasive polymorphisms appearance damaging health, cognitive, and behavioral processes in later life. OT is a major regulator of oxidative stress radicals that plays a major role in neonatal maturation of the central nervous system and many peripheral tissues expressing oxytocin/oxytocin-receptor (OT/OTR) system in the early postnatal period...
September 20, 2016: Biochimica et Biophysica Acta
Valentina Colonnello, Nicola Petrocchi, Marina Farinelli, Cristina Ottaviani
In recent years, a growing interest has emerged in the beneficial effects of positive social interactions on health. The present work aims to review animal and human studies linking social interactions and health throughout the lifespan, with a focus on current knowledge of the possible mediating role of opioids and oxytocin. During the prenatal period, a positive social environment contributes to regulating maternal stress response and protecting the fetus from exposure to maternal active glucocorticoids. Throughout development, positive social contact with the caregiver acts as a "hidden regulator" and promotes infant neuro affective development...
August 16, 2016: Current Neuropharmacology
Türkan Yurtsever, Thomas M Schilling, Monika Kölsch, Jonathan D Turner, Jobst Meyer, Hartmut Schächinger, Andrea B Schote
The physiological stress system and the circadian clock system communicate with each other at different signaling levels. The steroid hormone cortisol, the end-effector of the hypothalamus-pituitary-adrenal axis, is released in response to stress and acts as a mediator in circadian rhythms. We determined the effect of escalating cortisol doses on the expression of PERIOD genes (PER1, PER2 and PER3) in healthy subjects and analyzed whether the glucocorticoid receptor (GR) is involved in the cortisol-mediated PERIOD gene expression...
2016: Chronobiology International
A S Thakur, G P Littaru, I Funahashi, U S Painkara, N S Dange, P Chauhan
In neuroendocrine system the increase in oxidative status is produced by a glucocorticoid-dependent and transcriptional increase in pro-oxidative drive, with concurrent inhibition of the antioxidant defense system, ultimately leading to increased neuronal cell death. Functional hypothalamic disturbances and neuroendocirne aberrations have both short and long term consequences for reproductive health. Understandably, an impaired or diminished hypothalamic-pituitary-ovarian axis leads to anovulation and hypoestrogenism...
July 2016: Indian Journal of Clinical Biochemistry: IJCB
Michael D Weber, Jonathan P Godbout, John F Sheridan
Mounting evidence indicates that pro-inflammatory signaling in the brain affects mood, cognition, and behavior and is linked with the etiology of psychiatric disorders, including anxiety and depression. The purpose of this review is to focus on stress-induced bi-directional communication pathways between the CNS and peripheral immune system that converge to promote a heightened neuroinflammatory environment. These communication pathways involve sympathetic outflow from the brain to the peripheral immune system that biases hematopoietic stem cells to differentiate into a glucocorticoid resistant and primed myeloid lineage immune cell...
June 20, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Shirley Alteba, Nachshon Korem, Irit Akirav
Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES. Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorders. Here we examined whether cannabinoids administered during "late adolescence" (extensive cannabis use in humans at the ages 18-25) could reverse the long-term adverse effects of ES on neurocognitive function in adulthood...
July 2016: Learning & Memory
Ludmila Filaretova, Tatiana Bagaeva
The brain and the gut interact bi-directionally through the brain-gut axis. The interaction is mediated by of the autonomic nervous system and by the hypothalamic-pituitary-adrenocortical (HPA) system. The first brilliant demonstration of the brain-gut interactions was the cephalic phase of gastric and pancreatic secretion followed later by further brilliant demonstration, namely a conditional reflex, both discovered by Ivan Pavlov, the first physiologist who was awarded the Nobel Prize for Physiology or Medicine in 1904...
June 13, 2016: Current Neuropharmacology
Menahem B Doura, Ellen M Unterwald
Exposure to stress increases vulnerability to drug abuse, as well as relapse liability in addicted individuals. Chronic drug use alters stress response in a manner that increases drug seeking behaviors and relapse. Drug exposure and withdrawal have been shown to alter stress responses, and corticosteroid mediators of stress have been shown to impact addiction-related brain function and drug-seeking behavior. Despite the documented interplay between stress and substance abuse, the mechanisms by which stress exposure and drug seeking interact remain largely unknown...
2016: Frontiers in Cellular Neuroscience
Caroline Ménard, Madeline L Pfau, Georgia E Hodes, Scott J Russo
Diagnostic criteria for mood disorders including major depressive disorder (MDD) largely ignore biological factors in favor of behavioral symptoms. Compounding this paucity of psychiatric biomarkers is a need for therapeutics to adequately treat the 30-50% of MDD patients who are unresponsive to traditional antidepressant medications. Interestingly, MDD is highly prevalent in patients suffering from chronic inflammatory conditions, and MDD patients exhibit higher levels of circulating pro-inflammatory cytokines...
July 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ping Gan, Ze-Yang Ding, Cheng Gan, Rong-Rong Mao, Heng Zhou, Lin Xu, Qi-Xin Zhou
Stressful events can generate enduring memories, which may induce certain psychiatric disorders such as post-traumatic stress disorder (PTSD). However, the underlying molecular mechanisms in these processes remain unclear. In this study, we examined whether the active form of the small G protein Rac1, Rac1-GTP, is involved in fear memory. Firstly, we detected the time course changes of Rac1-GTP after foot shocks (a strong stressor) and exogenous corticosterone (CORT) treatment. The data showed that stress and CORT induced the downregulation of Rac1-GTP in the hippocampus...
September 2016: Psychoneuroendocrinology
Brent Myers, Jessie R Scheimann, Ana Franco-Villanueva, James P Herman
In response to stress, defined as a real or perceived threat to homeostasis or well-being, brain systems initiate divergent physiological and behavioral processes that mobilize energy and promote adaptation. The brainstem contains multiple nuclei that engage in autonomic control and reflexive responses to systemic stressors. However, brainstem nuclei also play an important role in neuroendocrine responses to psychogenic stressors mediated by the hypothalamic-pituitary-adrenocortical axis. Further, these nuclei integrate neuroendocrine responses with stress-related behaviors, significantly impacting mood and anxiety...
May 18, 2016: Neuroscience and Biobehavioral Reviews
Rebecca Dumbell, Olga Matveeva, Henrik Oster
In mammals, molecular circadian clocks are present in most cells of the body, and this circadian network plays an important role in synchronizing physiological processes and behaviors to the appropriate time of day. The hypothalamic-pituitary-adrenal endocrine axis regulates the response to acute and chronic stress, acting through its final effectors - glucocorticoids - released from the adrenal cortex. Glucocorticoid secretion, characterized by its circadian rhythm, has an important role in synchronizing peripheral clocks and rhythms downstream of the master circadian pacemaker in the suprachiasmatic nucleus...
2016: Frontiers in Endocrinology
Gretchen E Tietjen, Dawn C Buse, Stuart A Collins
Maltreatment during childhood increases vulnerability to a host of health disorders, including migraine. Putative mechanisms linking maltreatment and migraine include stress-induced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, as well as disruption of other stress-mediating homeostatic systems, including those involving endocannabinoids, monoamine neurotransmitters, oxytocin, and inflammation. Prolonged elevation of glucocorticoids alters the neural architecture of the limbic system, resulting in the structural as well as functional changes described in both maltreatment and in migraine...
July 2016: Current Treatment Options in Neurology
Valerie L Kinner, Oliver T Wolf, Christian J Merz
Dysfunctional reward processing is known to play a central role for the development of psychiatric disorders. Glucocorticoids that are secreted in response to stress have been shown to attenuate reward sensitivity and thereby might promote the onset of psychopathology. However, the underlying neurobiological mechanisms mediating stress hormone effects on reward processing as well as potential sex differences remain elusive. In this neuroimaging study, we administered 30mg cortisol or a placebo to 30 men and 30 women and subsequently tested them in the Monetary Incentive Delay Task...
August 2016: Hormones and Behavior
Ruili Dang, Yujin Guo, Ling Zhang, Lei Chen, Ranyao Yang, Pei Jiang
Exposure to chronic stress or excess glucocorticoids is associated with the development of depression and heart disease, but the underlying mechanisms remain equivocal. While recent evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an essential role in cardiac function, much is still unknown concerning the biological link between NRG1/ErbB pathway and the stress-induced comorbidity of depression and cardiac dysfunction. Therefore, we examined the protein expression of NRG1 and ErbB receptors in the myocardium of rats following chronic unpredictable mild stress (CUMS) or rats treated with two different doses (0...
August 2016: Steroids
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